Neuro-oxidative stress mediated by reactive oxygen and nitrogen species has been widely implicated in the pathogenesis of Parkinson's disease(PD).Polydeoxyribonucleotide(PDRN),a DNA-derived biopolymer with reporte...Neuro-oxidative stress mediated by reactive oxygen and nitrogen species has been widely implicated in the pathogenesis of Parkinson's disease(PD).Polydeoxyribonucleotide(PDRN),a DNA-derived biopolymer with reported anti-inflammatory properties,has not been fully explored in the context of PD.In this study,PDRN purified from heat-inactivated Enterococcus faecium FBL1(HEF PDRN)was structurally characterized by electrophoresis and Fourier transform infrared spectroscopy.Its cytoprotective effects were evaluated in MPTPinduced SH-SY5Y and C2C12 cells,and its in vivo effects were examined in an MPTP-induced PD mouse model using behavioral assays,histological analysis,transcriptomics,and molecular profiling.HEF PDRN treatment was associated with improved motor performance in rotarod,grip strength,and wire-hanging tests,as well as reduced immobility in the forced swim test.Histological and immunohistochemical analyses indicated attenuation of MPTP-induced muscle damage,preservation of dopaminergic neurons,and reducedα-synuclein aggregation.Transcriptomic analysis revealed attenuation of MPTP-induced suppression of neuroprotective(Park7,and Sqstm1),myogenic(Myf5,MyoG,and Myh1),and osteogenic-associated(Bmp2,Runx2,and Wnt5b)gene expression,with enrichment of Wnt/β-catenin and BMP/SMAD signaling pathways.These effects were accompanied by modulation of MAPK signaling and activation of the adenosine A2A receptor,together with changes inβ-catenin levels.Overall,HEF PDRN may represent a food fermentation-derived bioactive compound associated with antioxidant and anti-inflammatory signaling responses,along with modulation of MAPKmediated BMP/SMAD/Wnt pathways,under neuro-oxidative stress.These findings suggest its potential relevance for the development of functional food ingredients targeting neuroprotective and neuromuscularassociated responses within an acute neurotoxicity model.展开更多
基金supported by the National Research Foundation of the Republic of Korea(NRF)grant funded by the Republic of the Korean Government(MSIT)(RS-2023-NR077274).
文摘Neuro-oxidative stress mediated by reactive oxygen and nitrogen species has been widely implicated in the pathogenesis of Parkinson's disease(PD).Polydeoxyribonucleotide(PDRN),a DNA-derived biopolymer with reported anti-inflammatory properties,has not been fully explored in the context of PD.In this study,PDRN purified from heat-inactivated Enterococcus faecium FBL1(HEF PDRN)was structurally characterized by electrophoresis and Fourier transform infrared spectroscopy.Its cytoprotective effects were evaluated in MPTPinduced SH-SY5Y and C2C12 cells,and its in vivo effects were examined in an MPTP-induced PD mouse model using behavioral assays,histological analysis,transcriptomics,and molecular profiling.HEF PDRN treatment was associated with improved motor performance in rotarod,grip strength,and wire-hanging tests,as well as reduced immobility in the forced swim test.Histological and immunohistochemical analyses indicated attenuation of MPTP-induced muscle damage,preservation of dopaminergic neurons,and reducedα-synuclein aggregation.Transcriptomic analysis revealed attenuation of MPTP-induced suppression of neuroprotective(Park7,and Sqstm1),myogenic(Myf5,MyoG,and Myh1),and osteogenic-associated(Bmp2,Runx2,and Wnt5b)gene expression,with enrichment of Wnt/β-catenin and BMP/SMAD signaling pathways.These effects were accompanied by modulation of MAPK signaling and activation of the adenosine A2A receptor,together with changes inβ-catenin levels.Overall,HEF PDRN may represent a food fermentation-derived bioactive compound associated with antioxidant and anti-inflammatory signaling responses,along with modulation of MAPKmediated BMP/SMAD/Wnt pathways,under neuro-oxidative stress.These findings suggest its potential relevance for the development of functional food ingredients targeting neuroprotective and neuromuscularassociated responses within an acute neurotoxicity model.
